Studies of the in vitro tactoid formation of sickle cell hemoglobin are planned. The in vitro behavior of HbS alone and of HbS hybrids with HbC, HbD and HbO will be measured by light scattering, a technique which allows continuous observations of tactoid formation as a function of time. The effect upon tactoid formation kinetics of inhibitors such as cyanate, urea, carbamyl phosphate, and reagents being synthesized by other investigators in the Boston Sickle Cell Center will be studied. The effect of these reagents upon other blood proteins will be measured. The effect of all the above reagents on the three dimensional structure of HbS will be measured by biophysical methods such as difference spectroscopy, difference circular dichroism, and spectrofluorimetry. The objectives of this research are to evaluate the tactoid formation of HbS as a function of time by observing it in vitro when HbS alone and HbS in combination with HbC, HbD, or HbO are reacting. The effect of reagents which can inhibit sickling can then be evaluated, as can their effect on other components of the blood which would be exposed to such reagents in clinical treatment. It is hoped that such data will expedite the development of better therapeutic modalities for patients with sickle cell anemia or other sickle cell diseases, with emphasis on those which can slow the aggregation of HbS and thus avoid the onset of sickle cell crises. BIBLIOGRAPHIC REFERENCE: Chapman, C.E. and E.R. Simons, Conformational changes induced by addition of carbamyl phosphate to sickle cell hemoglobin. Blood 46, 1052 (1975).